The aim of this project is the development of reproducible in vitro models for the study of neuronal and glial pathology. Continued effort will be maintained in carrying out the projects outlined in the original application. 1. Hypoxia: Effect of chronic hypoxia on CNS cultures (cerebellum and neocortex) will be studied using light and electron microscopy. (Effect of acute hypoxia on CNS cultures has been studied previously). 2. Cholesterol biosynthesis inhibitor: Effect of a cholesterol biosynthesis inhibitor, 20,25-diazacholesterol on CNS cultures, particularly a possible effect on myelin formation in vitro, will be investigated. (Effect of AY9944, another cholesterol synthesis inhibitor on CNS cultures, has been studied and reported previously). 3. Acrylamide: The neurotoxic effect of acrylamide will be studied in cultures of PNS (dorsal root ganglia) and CNS (spinal cord) using light and electron microscopy.